Greatwall maintains mitosis through regulation of PP2A

EMBO J. 2009 Sep 16;28(18):2786-93. doi: 10.1038/emboj.2009.228. Epub 2009 Aug 13.

Abstract

Greatwall (GW) is a new kinase that has an important function in the activation and the maintenance of cyclin B-Cdc2 activity. Although the mechanism by which it induces this effect is unknown, it has been suggested that GW could maintain cyclin B-Cdc2 activity by regulating its activation loop. Using Xenopus egg extracts, we show that GW depletion promotes mitotic exit, even in the presence of a high cyclin B-Cdc2 activity by inducing dephosphorylation of mitotic substrates. These results indicate that GW does not maintain the mitotic state by regulating the cyclin B-Cdc2 activation loop but by regulating a phosphatase. This phosphatase is PP2A; we show that (1) PP2A binds GW, (2) the inhibition or the specific depletion of this phosphatase from mitotic extracts rescues the phenotype induced by GW inactivation and (3) the PP2A-dependent dephosphorylation of cyclin B-Cdc2 substrates is increased in GW-depleted Xenopus egg extracts. These results suggest that mitotic entry and maintenance is not only mediated by the activation of cyclin B-Cdc2 but also by the regulation of PP2A by GW.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Male
  • Microcystins / metabolism
  • Mitosis*
  • Models, Biological
  • Okadaic Acid / metabolism
  • Oocytes / metabolism
  • Phenotype
  • Phosphorylation
  • Protein Phosphatase 2 / metabolism*
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / physiology*
  • Spermatozoa / metabolism
  • Xenopus Proteins / chemistry
  • Xenopus Proteins / physiology*
  • Xenopus laevis / metabolism*

Substances

  • Microcystins
  • Xenopus Proteins
  • Okadaic Acid
  • microcystin
  • MASTL protein, Xenopus
  • Protein-Serine-Threonine Kinases
  • Protein Phosphatase 2